Universität zu Köln

Schumacher, Christian Eric, Rausch, Marvin ORCID: 0000-0003-1562-4337, Greven, Tobias, Neudorfl, Joerg-Martin, Schneider, Tanja and Schmalz, Hans-Guenther ORCID: 0000-0003-0489-1827 (2022). Total Synthesis and Antibiotic Properties of Amino-Functionalized Aromatic Terpenoids Related to Erogorgiaene and the Pseudopterosins. Eur. J. Org. Chem., 2022 (26). WEINHEIM: WILEY-V C H VERLAG GMBH. ISSN 1099-0690

Full text not available from this repository.

Abstract

Following a concept recently introduced by Hergenrother,([6]) the present study addresses the question of whether certain antimicrobially active aromatic (marine) natural products can be converted into more potent broad-spectrum antibiotics by introducing an aminoalkyl side chain. To this end, phenolic mono- and sesquiterpenoids (incl. carvacrol, xanthorrhizol, and 7-hydroxycalamene) as well as the diterpenes 7-hydroxyerogorgiaene and 9-deoxypseudopterosin A were converted into amino-functionalized analogs that display either an amino-methyl or a 2-amino-ethoxy substituent in place of (or next to) the OH group. This was achieved either by Pd-catalyzed nitromethylation/reduction of the aryltriflates, by O-alkylation of the phenols with bromoacetonitrile and subsequent reduction, or by ortho-hydroxymethylation/amination. During the study, an efficient enantioselective total synthesis of 7-hydroxyerogorgiaene (8 steps, 29 % overall yield) and 9-deoxypseudopterosin A (9 steps, 30 % overall yield) was elaborated using an asymmetric cobalt-catalyzed hydrovinylation (91 % ee) of 3-methoxy-4-methyl-styrene as the chirogenic step. Other important C-C bond forming steps include a Pd-catalyzed Suzuki cross-coupling and diastereoselective Lewis acid-mediated cyclization reactions. A total of 16 amino derivatives of natural products were prepared and subsequently tested for their antibacterial properties. Some of the diterpene-derived amines showed high efficacy, not only against Gram-positive (S. aureus SG511, S. aureus HG003, B. subtilis 168; MIC=0.5 to 2 mu g/ml), but also against Gram-negative bacterial strains (E. coli K12; E. coli I-11276b; MIC=8 to 32 mu g/ml). This clearly supported the underlying working hypothesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schumacher, Christian Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Rausch, Marvin UNSPECIFIED orcid.org/0000-0003-1562-4337 UNSPECIFIED Greven, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Neudorfl, Joerg-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Guenther UNSPECIFIED orcid.org/0000-0003-0489-1827 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-674344
DOI:	10.1002/ejoc.202200058
Journal or Publication Title:	Eur. J. Org. Chem.
Volume:	2022
Number:	26
Date:	2022
Publisher:	WILEY-V C H VERLAG GMBH
Place of Publication:	WEINHEIM
ISSN:	1099-0690
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTIMICROBIAL ACTIVITY; ESSENTIAL OILS; ENANTIOSELECTIVE SYNTHESIS; ANTIBACTERIAL ACTIVITY; SECO-PSEUDOPTEROSINS; DITERPENE-GLYCOSIDES; NATURAL-PRODUCTS; BAD BUGS; DERIVATIVES; CARVACROL Multiple languages Chemistry, Organic Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67434